The endocrine cells of the adrenal medulla are similar in many ways to sympathetic postganglionic neurons (see also ). They receive input from sympathetic preganglionic neurons, are excited by acetylcholine, and release catecholamines. However, the cells of the adrenal medulla differ from sympathetic postganglionic neurons in that they release catecholamines into the circulation rather than into a synapse. Moreover, the main catecholamine released is epinephrine, not norepinephrine. In humans, 80% of the catecholamine released by the adrenal medulla is epinephrine, and 20% is norepinephrine.
Some sympathetic postganglionic neurons release acetylcholine rather than norepinephrine as their neurotransmitter. For example, sympathetic postganglionic neurons that innervate eccrine sweat glands are cholinergic. The acetylcholine receptors involved are muscarinic, and they are therefore blocked by atropine. Similarly, some blood vessels are innervated by cholinergic sympathetic postganglionic neurons. In addition to releasing acetylcholine, the postganglionic neurons that supply the sweat glands also release neuropeptides, including calcitonin gene–related peptide and vasoactive intestinal polypeptide.
The neurotransmitter released by parasympathetic postganglionic neurons is acetylcholine. The effects of these neurons on various target organs are listed in
Table 11.1 . Parasympathetic postganglionic actions are mediated by muscarinic receptors. On the basis of binding studies, the action of selective antagonists, and molecular cloning, five types of muscarinic receptors have been identified (see
Chapter 6).
Activation of M1 receptors enhances the secretion of gastric acid in the stomach. M2 receptors are the most abundant receptor type in smooth muscle, including smooth muscle in the intestines, uterus, trachea, and bladder. In addition, they are present in autonomic ganglia and in the heart, where they exert negative chronotropic and inotropic actions (see
Chapter 18). M 3 receptors are also present in the smooth muscle of a variety of organs, and although they are less abundant than M2 receptors, normal contractile patterns appear to require an interaction between the two types of receptors. M4 receptors, like M2 receptors, are present in autonomic ganglia and thus play a role in synaptic transmission at these sites. M5 receptors are present in the sphincter muscle of the pupil, in the esophagus, and in the parotid gland, as well as in cerebral blood vessels.
Muscarinic receptors, like adrenergic receptors, have diverse actions. Some of their effects are mediated by specific second messenger systems. For example, cardiac M2 muscarinic receptors may act by way of the inositol triphosphate system, and they may also inhibit adenylyl cyclase and thus cAMP synthesis. Muscarinic receptors also open or close ion channels, particularly K+ or Ca++ channels. This action on ion channels is likely to occur through activation of G proteins. A third action of muscarinic receptors is to relax vascular smooth muscle by an effect on endothelial cells, which produce endothelium-derived relaxing factor (EDRF). EDRF is actually nitric oxide, a gas released when arginine is converted to citrulline by nitric oxide synthase (see ). Nitric oxide relaxes vascular smooth muscle by stimulating guanylate cyclase and thereby increasing levels of cyclic guanosine monophosphate (cGMP), which in turn activates a cGMP-dependent protein kinase (see ). The number of muscarinic receptors is regulated, and exposure to muscarinic agonists decreases the number of receptors by internalization of the receptors.